Lycodine-type alkaloids from Lycopodiastrum casuarinoides and their acetylcholinesterase inhibitory activity

Zheling Feng; Shixin Chen; Wei Wang; Lu Feng; Yanyan Dong; Yiping Zou; Changqiang Ke; Chunping Tang; Sheng Yao; Haiyan Zhang; Lishe Gan; Yang Ye; Ligen Lin

doi:10.1016/j.fitote.2019.104378

Lycodine-type alkaloids from Lycopodiastrum casuarinoides and their acetylcholinesterase inhibitory activity

Fitoterapia. 2019 Nov:139:104378. doi: 10.1016/j.fitote.2019.104378. Epub 2019 Oct 30.

Authors

Zheling Feng¹, Shixin Chen², Wei Wang³, Lu Feng⁴, Yanyan Dong⁵, Yiping Zou⁵, Changqiang Ke⁴, Chunping Tang⁴, Sheng Yao⁴, Haiyan Zhang³, Lishe Gan⁶, Yang Ye⁷, Ligen Lin⁸

Affiliations

¹ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
² College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310007, China.
³ CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁴ State Key Laboratory of Drug Research, & Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁵ College of Chemistry and Bioengineering, Yichun University, Yichun, Jiangxi 336000, China.
⁶ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310007, China. Electronic address: lsgan@zju.edu.cn.
⁷ State Key Laboratory of Drug Research, & Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China. Electronic address: yye@simm.ac.cn.
⁸ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China. Electronic address: ligenl@um.edu.mo.

PMID: 31676395
DOI: 10.1016/j.fitote.2019.104378

Abstract

Five previously undescribed lycodine-type alkaloids, named huperzine Y (1), 8,15-epoxy-N-demethylhuperzinine (2), 7-hydroxyl-huperzinine (3), huperzine Z (4), and huperzine D N-oxide (5), were isolated from the aerial parts and roots of Lycopodiastrum casuarinoides (Lycopodiaceae), along with ten known analogues. The structures of the new compounds were elucidated by means of spectroscopic technique (IR, UV, MS and NMR). The absolute configurations of the new compounds were established on the basis of comparison of their experimental and TD-DFT (time-dependent density functional theory) calculated ECD spectra. Moreover, all the isolates were evaluated for acetylcholinesterase (AChE) inhibitory activity. Only huperzine C showed moderate activity, with an IC₅₀ value of 0.525 ± 0.140 μM, which was comparable with the positive control, huperzine A (IC₅₀ = 0.143 ± 0.029 μM).

Keywords: ECD; Lycodine-type alkaloids; Lycopodiaceae; Lycopodiastrum casuarinoides; TD-DFT.

MeSH terms

Alkaloids / isolation & purification
Alkaloids / pharmacology*
China
Cholinesterase Inhibitors / isolation & purification
Cholinesterase Inhibitors / pharmacology*
Heterocyclic Compounds, 4 or More Rings / isolation & purification
Heterocyclic Compounds, 4 or More Rings / pharmacology*
Lycopodiaceae / chemistry*
Molecular Structure
Phytochemicals / isolation & purification
Phytochemicals / pharmacology
Plant Components, Aerial / chemistry
Plant Roots / chemistry

Substances

Alkaloids
Cholinesterase Inhibitors
Heterocyclic Compounds, 4 or More Rings
Phytochemicals
lycodine